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free120/Block 3/Question#27

A 30-year-old woman comes to the physician because ...

The second CFTR mutation was not detected by the testing obtained

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Cystic fibrosis is an autosomal recessive disease involving CFTR (which encodes the CFTR protein), which means you need a double hit to express the disease. If the genetic test only picked up one, then it must have missed the other.

drdoom  The reason something is an “autosomal recessive” disease is because the protein encoded by the gene (of which you have two alleles, remember) does something where as long as you make SOME protein, your body should be okay. That’s kind of vague, so take the case of Cystic Fibrosis: you don’t present with Cystic Fibrosis if you have at least one functional allele -- that’s because CFTR protein is a protein that (in the case of bronchiole tissue) moves Chloride ion from inside cells to the outside lumen, which brings with it H2O and keeps the bronchiole lumen nice and watery, and fluid and non-viscous and non-pluggy. So long as you make enough of this protein, you don’t “need” both alleles to be good; the good allele can “make up for” (make enough of the protein product) to compensate for the “broken allele.” So, once again, understanding the pathophys of a disease allows you to reason through and predict things like disease penetrance and expressivity. +  




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submitted by drdoom(211),

The reason something is an “autosomal recessive” disease is because the protein encoded by the gene (of which you have two alleles, of course) does something where as long as you make SOME protein, your body should be okay.

That’s kind of vague, so take the case of Cystic Fibrosis: you don’t present with Cystic Fibrosis if you have at least one functional allele -- that’s because CFTR protein is a protein that (in the case of bronchiole tissue) moves Cl- from inside cells to the outside lumen, which brings with it H2O and keeps the bronchiole lumen nice and watery, and fluid and non-viscous and non-pluggy.

So long as you make enough of this protein, you don’t “need” both alleles to be good; the good allele can “make up for” (make enough of the protein product to compensate for) the “broken allele.” So, once again, understanding the pathophys of a disease allows you to reason through and predict things like disease penetrance and expressivity.